The objective is to understand how different collagens are made and interact to form connective tissues. We found that the precursors of collagens, procollagens, bear propeptides at both amino and carboxyl ends, and that separate enzymes, called amino and carboxyl procollagen peptidases cleave them sequentially. Now we shall characterize these enzymes, find where they act and how they influence collagen fiber formation at the cell surface. We also want to find out how triple-stranded procollagen molecules are assembled inside cells and are then secreted. Other components of connective tissue, such as proteoglycans and fibronectin, are also secreted by specialized connective tissue cells and we want to know their relationship to collagen fiber formation. We shall study the biosynthesis of fibronectin and the interaction of isolated fibronectin with collagen. There are genetically different procollagens. We have partly characterized procollagen III of chick embryo blood vessels and found other larger putative procollagens. We shall compare them with procollagens made by smooth muscle and find out whether they are precursors to recently described new collagens. In a separate investigation we are finding out how human vascular endothelial cells make basement membrane collagens. Overall, we shall find out how different procollagens are made and processed how they interact in bone, tendon, cartilage, blood vessels and smooth muscle during development. This will contribute to understanding of problems in wound healing, and in normal and pathological growth and repair.